The 20-valent pneumococcal conjugate vaccine (PCV20): expected added value.

OBJECTIVES: Currently existing pneumococcal vaccines have contributed to a major reduction in pneumococcal disease. However, there remains an unmet need for vaccine coverage of serotypes not included in PCV13 to further reduce the burden of disease. The objective of this review is to assess the potential impact of implementation of the investigational 20-valent pneumococcal conjugate vaccine (PCV20) in the childhood and adult immunization programme in Belgium and Europe. METHODS: A literature search was conducted to identify publications and surveillance reports concerning the effectiveness and safety of pneumococcal vaccines, epidemiological data on pneumococcal disease or serotype distribution dynamics after introduction of systematic vaccination. RESULTS: Serotypes included in PCV20 currently account for the majority of pneumococcal disease in Belgium and Europe. In Belgium, PCV20-serotypes accounted for 71.4% of invasive pneumococcal disease (IPD) cases across all age groups in 2019, of which 39.2% were caused by PCV20-non-PCV13-serotypes. In Europe, these seven serotypes accounted for 37,6% of IPD cases in 2018.  PCV20 has proven to be well tolerated in vaccine-naïve adults and elicits a substantial immune response against all serotypes included. CONCLUSION: Due to serotype replacement following the introduction of PCV7 and PCV13, a considerable proportion of pneumococcal disease is currently caused by PCV20-serotypes. PCV20 has the potential of preventing more pneumococcal disease in children and the adult population at risk than the existing conjugate vaccines. The available evidence on safety and immunogenicity of PCV20 is promising, but further research is needed to provide data about vaccine effectiveness, immune response duration and replacement phenomenon after introduction of PCV20.

Clinical Efficacy of Temocillin Standard Dosing in Patients Treated with Outpatient Antimicrobial Therapy.

In 2020, EUCAST introduced breakpoints for temocillin. Based on these guidelines, reporting of temocillin susceptibility of Enterobacterales in the context of complicated urinary tract infections (cUTI) implicates the use of a high dose of temocillin (2 g q8h) constantly. We aimed to evaluate the clinical outcome of patients treated with the standard dose (4 g/day) of temocillin in outpatient parenteral antimicrobial therapy (tOPAT). Demographics, clinical and treatment parameters, and late clinical cure (at day 30 after tOPAT completion) were recorded. Univariate generalised estimating equation analyses, with clinical cure as outcome variable, were performed to evaluate covariate associations. Fifty-seven tOPAT episodes in 50 patients were included with a median antimicrobial treatment duration of 21 (range 10-228) days, and cUTI was the main indication (87.7%). Late clinical cure was achieved in 85.7% of the tOPAT episodes. Non-disseminated infections and minimal inhibitory concentrations (MIC) values ≤ 8 mg/L were associated with good late clinical outcome. In conclusion, a standard temocillin dose (4 g/day) results in good clinical outcomes in the treatment of cUTIs in tOPAT patients. Therefore, our centre concluded that the use of standard temocillin dosing should be continued instead of the high dose for cUTI in non-critically ill patients infected with Enterobacterales with an MIC ≤ 4 mg/L.

Characterization of Emerging Serotype 19A Pneumococcal Strains in Invasive Disease and Carriage, Belgium.

After switching from 13-valent to 10-valent pneumococcal conjugate vaccine (PCV10) (2015-2016) for children in Belgium, we observed rapid reemergence of serotype 19A invasive pneumococcal disease (IPD). Whole-genome sequencing of 166 serotype 19A IPD isolates from children (n = 54) and older adults (n = 56) and carriage isolates from healthy children (n = 56) collected after the vaccine switch (2017-2018) showed 24 sequence types (STs). ST416 (global pneumococcal sequence cluster [GPSC] 4) and ST994 (GPSC146) accounted for 75.9% of IPD strains from children and 65.7% of IPD (children and older adults) and carriage isolates in the PCV10 period (2017-2018). These STs differed from predominant 19A IPD STs after introduction of PCV7 (2011) in Belgium (ST193 [GPSC11] and ST276 [GPSC10]), which indicates that prediction of emerging strains cannot be based solely on historical emerging strains. Despite their susceptible antimicrobial drug profiles, these clones spread in carriage and IPD during PCV10 use.

End-users feedback and perceptions associated with the implementation of a clinical-rule based Check of Medication Appropriateness service.

BACKGROUND: To support appropriate prescribing hospital-wide, the 'Check of Medication Appropriateness' (CMA) service was implemented at the University Hospitals Leuven. The CMA concerns a clinical rule based and pharmacist-led medication review service. The aim of this study was to explore both physicians' and pharmacists' feedback on the optimised CMA service to further improve the service. METHODS: An anonymous e-questionnaire was sent to all physicians active in the University Hospitals Leuven (n = 1631) and to all clinical pharmacists performing the CMA service (n = 16). Feedback was collected using multiple choice questions. During a 5-month period, physicians were also contacted in case of non-acceptance of recommendations to investigate barriers affecting implementation. Thematic analysis was performed and additional acceptance after telephone contact within 24 h was registered. RESULTS: A total of 119 physicians (7.3%) and 16 pharmacists (100%) completed the e-questionnaire. The overall service was assessed as clinically relevant to highly relevant by 77.7% of physicians. The main reasons for non-acceptance of recommendations were related to workload, work environment and time constraints. About two thirds (66.3%) of initially not-accepted recommendations were accepted after phone contact. A nearly full consensus was reached among pharmacists (15/16) on the centralised CMA being complementary to current clinical pharmacy activities. Two major barriers were reported by pharmacists: (1) too limited time allocation and (2) a large number of irrelevant alerts. CONCLUSIONS: The CMA was perceived as clinically relevant by the majority of end-users. Acceptance rate of pharmaceutical recommendations was further increased by calling the physician. Increasing the specificity of clinical rules in the future is imperative.

Systematic Comparison of Hospital-Wide Standard and Model-Based Therapeutic Drug Monitoring of Vancomycin in Adults.

We aimed to evaluate the predictive performance and predicted doses of a single-model approach or several multi-model approaches compared with the standard therapeutic drug monitoring (TDM)-based vancomycin dosing. We performed a hospital-wide monocentric retrospective study in adult patients treated with either intermittent or continuous vancomycin infusions. Each patient provided two randomly selected pairs of two consecutive vancomycin concentrations. A web-based precision dosing software, TDMx, was used to evaluate the model-based approaches. In total, 154 patients contributed 308 pairs. With standard TDM-based dosing, only 48.1% (148/308) of all of the second concentrations were within the therapeutic range. Across the model-based approaches we investigated, the mean relative bias and relative root mean square error varied from -5.36% to 3.18% and from 24.8% to 28.1%, respectively. The model averaging approach according to the squared prediction errors showed an acceptable bias and was the most precise. According to this approach, the median (interquartile range) differences between the model-predicted and prescribed doses, expressed as mg every 12 h, were 113 [-69; 427] mg, -70 [-208; 120], mg and 40 [-84; 197] mg in the case of subtherapeutic, supratherapeutic, and therapeutic exposure at the second concentration, respectively. These dose differences, along with poor target attainment, suggest a large window of opportunity for the model-based TDM compared with the standard TDM-based vancomycin dosing. Implementation studies of model-based TDM in routine care are warranted.

Clinical Efficacy and Safety of Vancomycin Continuous Infusion in Patients Treated at Home in an Outpatient Parenteral Antimicrobial Therapy Program.

Vancomycin is commonly used in outpatient parenteral antimicrobial therapy (OPAT) of Gram-positive infections. Therapeutic drug monitoring and adverse event monitoring pose a challenge. Outcome data of vancomycin in OPAT (vOPAT) are limited. The study aim was to report the safety and efficacy of a structured vOPAT program implemented in the University Hospitals Leuven. The program provides continuous elastomeric infusion of vancomycin at home with biweekly follow-up at the outpatient clinic. Demographics, clinical, biochemical and treatment parameters, target attainment parameters and clinical outcomes were recorded. An e-survey was conducted to assess patient satisfaction. Thirty-five vOPAT episodes in 32 patients were included. During 206 follow-up consultations, 203 plasma concentration measurements were registered with a median vancomycin plasma concentration of 22.5 mg/L (range 6.6-32.0). The majority of concentrations (68.5%) were within the therapeutic range (20.0-25.0 mg/L). Adverse event rates, including drug- (5.7%) and catheter-related (5.7%) events, were low. For 32 vOPAT episodes, a clinical cure rate of 100% was observed. All patients who completed the e-survey were satisfied with their vOPAT course. These findings show that a structured vOPAT program with rigorous follow-up provides safe and effective ambulatory treatment of patients with vancomycin in continuous infusion.

From basic to advanced computerised intravenous to oral switch for paracetamol and antibiotics: an interrupted time series analysis.

OBJECTIVES: Early switch from intravenous to oral therapy of bioequivalent drugs has major advantages but remains challenging. At our hospital, a basic clinical rule was designed to automatically alert the physician to review potential intravenous to oral switch (IVOS). A rather low acceptance rate was observed. In this study, we aimed to develop, validate and investigate the effect of more advanced clinical rules for IVOS, as part of a centralised pharmacist-led medication review service. DESIGN AND SETTING: A quasi-experimental study was performed in a large teaching hospital in Belgium using an interrupted time series design. INTERVENTION: A definite set of 13 criteria for IVOS, focusing on the ability of oral absorption and type of infection, was obtained by literature search and validated by a multidisciplinary expert panel. Based on these criteria, we developed a clinical rule for paracetamol and one for ten bioequivalent antibiotics to identify patients with potentially inappropriate intravenous prescriptions (PIVs). Postintervention, the clinical rule alerts were reviewed by pharmacists, who provided recommendations to switch in case of eligibility. PRIMARY AND SECONDARY OUTCOME MEASURES: A regression model was used to assess the impact of the intervention on the number of persistent PIVs between the preintervention and the postintervention period. The total number of recommendations, acceptance rate and financial impact were recorded for the 8-month postintervention period. RESULTS: At baseline, a median number of 11 (range: 7-16) persistent PIVs per day was observed. After the intervention, the number reduced to 3 (range: 1-7) per day. The advanced IVOS clinical rules showed an immediate relative reduction of 79% (incidence rate ratio=0.21, 95% CI 0.13 to 0.32; p<0.01) in the proportion of persistent PIVs. No significant underlying time trends were observed during the study. Postintervention, 1091 recommendations were provided, of which 74.1% were accepted, resulting in a total 1-day cost saving of €4648.35. CONCLUSIONS: We showed the efficacy of advanced clinical rules combined with a pharmacist-led medication review for IVOS of bioequivalent drugs.

Safety and efficacy of phage therapy in difficult-to-treat infections: a systematic review.

According to the latest reports from WHO, the incidence of antibiotic-resistant bacterial infections is increasing worldwide, resulting in increased morbidity and mortality and a rising pressure on health-care systems. However, the development of new antibiotics is an expensive and time-consuming process, urging scientists to seek alternative antimicrobial strategies. Over the past few decades, the concept of therapeutic administration of bacteriophages (also known as phages) has gained popularity worldwide. Although conceptually promising, the widespread implementation of phage therapy in routine clinical practice is restricted by the scarcity of safety and efficacy data obtained according to the strict standards of the applicable clinical trial regulations. In this systematic review, we list clinical data published between Jan 1, 2000 and Aug 14, 2021 on the safety and efficacy of phage therapy for difficult-to-treat bacterial infections, and provide an overview of trials and case studies on the use of phage therapy in several medical disciplines.

Cost-effectiveness of check of medication appropriateness: methodological approach.

Background Adverse drug events following inappropriate prescribing in the hospital cause a substantial and avoidable medical and economic burden to hospitals, payers and patients alike. A clinical rule-based, pharmacist-led medication-review service, the 'Check of Medication Appropriateness' (CMA) was implemented in the University Hospitals Leuven. The CMA is shown to be effective in reducing potentially inappropriate prescriptions. Aim This study investigated whether this centralised clinical pharmacy service is cost-effective. Method We performed a cost-effectiveness analysis of three clinical rules of the CMA, targeting adverse drug events at three levels of severity: A) persistent opioid-induced constipation, B) ketorolac-induced gastrointestinal bleeding and C) drug-induced Torsade de Pointes. A decision tree was developed for each clinical rule. Both intervention costs as well as total costs associated with the occurrence of an adverse drug event were considered. The outcomes were reported in the form of an incremental cost-effectiveness ratio, expressed as an incremental cost per adverse drug event avoided. Results Applying clinical rules to avoid persistent opioid-induced constipation and ketorolac-induced gastrointestinal bleeding were cost-saving. Implementation of a medication check to avoid drug-induced Torsade de Pointes costed €8,846 per Torsade de Pointes avoided. Conclusion Our study provides strong indications that the CMA is worth its investment for clinical rules targeting (very) common adverse drug events, that can be avoided with limited expenses. Further research is required to assess the full CMA. The proposed model may be useful to perform cost-effectiveness analyses of other centralised clinical pharmacy services targeting inappropriate prescribing, at the level of individual adverse drug events.

Improving appropriate use of anticoagulants in hospitalised patients: A pharmacist-led Check of Medication Appropriateness intervention.

AIMS: Inappropriate anticoagulant use increases the risk of bleeding and thrombotic events. We implemented clinical decision rules to promote judicious medication use, as part of the 'Check of Medication Appropriateness' (CMA). The CMA is a pharmacist-led review service, targeting potentially inappropriate prescriptions (PIPs). In this analysis, we aimed to evaluate the impact of the CMA on anticoagulant prescribing. METHODS: The number of anticoagulant-related PIPs was evaluated before and after implementation of the intervention in a quasi-experimental interrupted time series analysis. The pre-implementation cohort received usual care. The anticoagulant-focused CMA, comprising 13 clinical rules pertaining to anticoagulation therapies, was implemented in the post-implementation cohort. Segmented regression analysis was used to assess the impact of the intervention on the number of residual PIPs. A residual PIP was defined as a PIP which persisted up to 48 hours after the CMA intervention. Total number of recommendations and acceptance rate were documented for the 2-year post-implementation period. RESULTS: Pre-implementation, we observed 501 PIPs in 466 inpatients on 36 days, with a median proportion of 78.5% (range: 46.2%-100%) residual PIPs per day. Post-implementation, 538 PIPs were detected in 485 patients over the same number of days. The CMA intervention reduced the median proportion to 18.2% (range: 0-100%) per day. The effect coincided with an immediate relative reduction of 70% (95%CI 0.19-0.46) in anticoagulant-related residual PIPs. Post-implementation, 2778 recommendations were provided and 75.1% were accepted. CONCLUSION: Our CMA approach significantly reduced anticoagulant-related PIPs. Implementing a pharmacist-led intervention, based on clinical rules, may support safer prescribing of anticoagulants.

Prospective assessment of breakthrough infections and neurotoxicity and their association with cefepime trough concentrations in patients with febrile neutropenia.

Cefepime is a first-line antibiotic for the treatment of febrile neutropenia (FN) in haematological cancer patients. Therapeutic drug monitoring (TDM) of cefepime is frequently advocated. However, it remains unclear what range of concentrations should be targeted for maximal efficacy and minimal toxicity. Therefore, we examined the relationship between cefepime exposure and clinical efficacy or neurotoxicity in FN patients. This prospective, observational, single-centre study included all adult hospitalised patients presenting with FN at the haematology ward and treated with cefepime from August 2019 until October 2020. Primary outcomes were incidence of breakthrough infection and neurotoxicity and their relationship with free cefepime serum trough concentrations. A total of 76 patients were included, contributing 96 cefepime treatment courses. The median (interquartile range) estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKD-EPI) and free cefepime trough concentration were 101 (85-112) mL/min/1.73m2 and 8.6 (4.9-16.2) mg/L, respectively. Interpatient and intrapatient variability in cefepime trough concentrations was largely explained by renal function. No cefepime-related breakthrough infections occurred during cefepime treatment. Neurotoxicity, probably induced by cefepime administration, occurred during 6/96 (6.3%) treatment courses. Patients with neurotoxicity showed a significant trend for higher trough concentrations (median 15.4 mg/L vs. 8.6 mg/L; P < 0.001). This study provides real-world clinical data showing that high cefepime dosage is efficacious and safe in FN patients. Routine TDM does not appear to be needed in FN patients with preserved renal function. However, TDM might be reserved for FN patients at high risk of cefepime-induced neurotoxicity or when intended to cover pathogens with a minimum inhibitory concentration >1 mg/L.

The effectiveness of Check of Medication Appropriateness for antimicrobial stewardship: an interrupted time series analysis.

OBJECTIVES: Inappropriate prescribing of antimicrobials in hospitals contributes to the emergence of resistance and adverse drug events. To support antimicrobial stewardship (AMS), clinical decision rules focusing on antimicrobial therapy were implemented in the 'Check of Medication Appropriateness' (CMA). The CMA is a hospital-wide pharmacist-led medication review service consisting of a clinical rule-based screening for potentially inappropriate prescriptions (PIPs). We aimed to investigate the impact of the CMA on antimicrobial prescribing. METHODS: An interrupted time series study was performed at the University Hospitals Leuven. The pre-implementation cohort was exposed to standard-of-care AMS. Afterwards, an AMS-focused CMA comprising 41 specific clinical rules, targeting six AMS objectives, was implemented in the post-implementation period. A regression model was used to assess the impact of the intervention on the number of AMS-related residual PIPs between both periods. The total number of recommendations and acceptance rate was recorded for the 2 year post-implementation period. RESULTS: Pre-implementation, a median proportion of 75% (range: 33%-100%) residual PIPs per day was observed. After the CMA intervention, the proportion was reduced to 8% (range: 0%-33%) per day. Use of clinical rules resulted in an immediate relative reduction of 86.70% (P < 0.0001) in AMS-related residual PIPs. No significant underlying time trends were observed during the study period. Post-implementation, 2790 recommendations were provided of which 81.32% were accepted. CONCLUSIONS: We proved that the CMA approach reduced the number of AMS-related residual PIPs in a highly significant and sustained manner, with the potential to further expand the service to other AMS objectives.

Concomitant Treatment with Voriconazole and Flucloxacillin: A Combination to Avoid.

BACKGROUND: Voriconazole is an antifungal drug used as one of the first-line treatments for invasive aspergillosis. This drug is extensively metabolized, predominantly via cytochrome P450 enzymes. An interaction between flucloxacillin and voriconazole, leading to subtherapeutic voriconazole concentrations, has previously been reported. We aimed to demonstrate that flucloxacillin independently influences voriconazole exposure. METHODS: Patients from three Belgian hospitals, treated with a combination of voriconazole and flucloxacillin, were included in this retrospective study. Voriconazole concentrations were collected both in a timeframe with and without flucloxacillin co-treatment. Multivariate analyses were performed to study the independent effect of flucloxacillin treatment on voriconazole exposure and the possible influence of the flucloxacillin dose. RESULTS: Thirty-three patients were included in this study and 145 trough concentrations (51 with, and 94 without concomitant flucloxacillin treatment) were analyzed. The median (IQR) voriconazole trough concentration sampled during flucloxacillin co-treatment was 0.5 (0-1.8) mg/L, whereas samples without flucloxacillin co-treatment had a median (IQR) voriconazole trough concentration of 3.5 (1.7-5.1) mg/L (p = 0.002), while receiving similar voriconazole doses. Subtherapeutic concentrations (<1 mg/L) were observed in 69% and 7% of the samples with flucloxacillin co-treatment versus samples without flucloxacillin co-treatment, respectively. CONCLUSION: This study shows that flucloxacillin co-treatment independently decreases voriconazole exposure. Caution is needed when these two drugs are administered simultaneously.

Fracture-related infection in long bone fractures: A comprehensive analysis of the economic impact and influence on quality of life.

OBJECTIVES: Fracture-related infection (FRI) is a feared complication with substantial clinical and economic consequences. The main objective of this study was to compare direct and indirect healthcare costs related to long bone fractures in patients with and without FRI and to assess its impact on the patient's quality of life (QoL). PATIENTS AND METHODS: Between January 2015 and March 2019, 175 patients with FRI were treated at the University Hospitals Leuven (Belgium). Using a matched-pair analysis, patients with an FRI were matched by age, sex, and fracture location (humeral, femoral, or tibial shaft) to a non-FRI cohort treated during the same time period. Clinical and process-related variables, direct hospital-related healthcare costs, and indirect costs due to absenteeism were compared between the two groups. Furthermore, the patient's QoL was evaluated using Patient-Reported Outcomes Measurement Information System (PROMIS) physical function and pain interference. RESULTS: After matched-pair analysis, 15 patients in both the FRI and non-FRI group were included. FRI was associated with direct hospital-related costs being eight times that of non-FRI patients (€ 47,845 [€ 43,072-€ 82,548] vs. € 5,983 [€ 4,519-€ 8,428], p < 0.001). Furthermore, FRI was associated with prolonged absenteeism (340 [340-676] vs. 86 [65-216] days, p = 0.007) and a median indirect cost that was nearly four times that of patients without FRI (€ 77,909 vs. € 19,706). Lastly, FRI patients showed significantly poorer outcomes on both physical function (35.6 vs. 48.4, p < 0.001) and pain interference (60.4 vs. 46.3, p < 0.001) PROMIS scales. CONCLUSION: Direct hospital-related healthcare costs of FRI are eight times that of non-FRI long bone fractures. Total healthcare costs are mainly driven by hospitalisation costs, wherein FRI is associated with prolonged length of stay. To the best of our knowledge, this study is the first to demonstrate that FRI is also associated with substantial absenteeism, which is almost four times higher compared to non-FRI patients. In addition to this economic impact, FRI significantly deteriorates QoL. Generalizing the outcome of this study should be done cautiously due to the small sample size of 15 patients in both the FRI and non-FRI group after matched-pair analysis.

Bacteriophage Therapy for Difficult-to-Treat Infections: The Implementation of a Multidisciplinary Phage Task Force (The PHAGEFORCE Study Protocol).

In times where only a few novel antibiotics are to be expected, antimicrobial resistance remains an expanding global health threat. In case of chronic infections caused by therapy-resistant pathogens, physicians have limited therapeutic options, which are often associated with detrimental consequences for the patient. This has resulted in a renewed interest in alternative strategies, such as bacteriophage (phage) therapy. However, there are still important hurdles that currently impede the more widespread implementation of phage therapy in clinical practice. First, the limited number of good-quality case series and clinical trials have failed to show the optimal application protocol in terms of route of administration, frequency of administration, treatment duration and phage titer. Second, there is limited information on the systemic effects of phage therapy. Finally, in the past, phage therapy has been applied intuitively in terms of the selection of phages and their combination as parts of phage cocktails. This has led to an enormous heterogeneity in previously published studies, resulting in a lack of reliable safety and efficacy data for phage therapy. We hereby present a study protocol that addresses these scientific hurdles using a multidisciplinary approach, bringing together the experience of clinical, pharmaceutical and molecular microbiology experts.

Timeliness of administration of amoxicillin-clavulanic acid and meropenem in a large tertiary care centre.

Background For amoxicillin-clavulanic acid and meropenem to be effective, concentrations must exceed the minimum inhibitory concentration of infecting pathogens. Objective To retrospectively evaluate time windows between both scheduled prescription and administration and reconstitution-preparation and end of administration of intravenous amoxicillin-clavulanic acid and meropenem prescriptions. Setting 37 hospital wards at a tertiary hospital, Belgium. Method All adult hospital stays with at least one amoxicillin-clavulanic acid or meropenem administration in 2018 were reviewed. Time windows were deemed acceptable if < 30 min between prescription and administration and < 90 or < 150 min between reconstitution-preparation and end of administration for amoxicillin-clavulanic acid and meropenem, respectively. Main outcome measure Time windows between prescription and administration and between reconstitution-preparation and administration. Results For 50 273 administered prescriptions, both time windows were acceptable in 53.7% of first dose and 56.4% of follow-up dose administrations. 43.7% of first doses did not respect the time window between reconstitution-preparation and administration (2.8%) or between prescription and administration (40.9%). These discrepancies equalled 11.1% and 26.3% for follow-up doses, respectively. Large variation across hospital wards was observed. After the first five consecutive administrations, 93.1% of patients had not received their antibiotics within the time windows allowed. The most striking predictor of timely administration with respect to both prescription and reconstitution-preparation time was prescription synchronisation with nursing administration rounds. Conclusion For amoxicillin-clavulanic acid and meropenem, timeliness of reconstitution-preparation and administration was appropriate in approximately half of administrations. Evaluating and safeguarding the timeliness of antibiotic administration should be considered an important aspect of antibiotic stewardship.

Spontaneous cervical swelling syndrome as a rare cause of neck edema: case series and literature review.

Spontaneous cervical swelling syndrome (SCSS) is a rare disorder characterized by unprovoked, self-limiting and often unilateral cervical edema. SCSS is a recurrent disorder that predominantly affects adult women and is not associated with laboratory abnormalities. We report on eight female patients with a mean age of 56 (38-82) years at the time of the first presentation. The episodes were characterized by an acute onset in all patients and had a mean duration of 3.8 (1-7) days. Biochemical analysis did not reveal any related abnormalities. Imaging of the neck and chest demonstrated diffuse edema in the supraclavicular fossa and left infrahyoid region in all patients. At the time of the acute event, lymphatic scintigraphy revealed tracer accumulation in the left supraclavicular region in three patients and could not demonstrate any abnormalities in the in-between episodes in two patients.

Long-term follow-up of patients with infective endocarditis in a tertiary referral center.

BACKGROUND: Infective endocarditis (IE) remains a severe disease with high mortality. Most studies report on short-term outcome while real world long-term outcome data are scarce. This study reports reinfection rates and mortality data during long-term follow-up. METHODS: A total of 270 patients meeting the modified Duke criteria for definite IE admitted to a tertiary care center between July 2000 and June 2007 were analyzed retrospectively. Early reinfection was defined as a new IE episode within 6 months; late reinfection as a new IE episode beyond 6 months follow-up. RESULTS: Median follow-up was 8.5 years. Early reinfection occurred in 10 patients (3.7%), late reinfection in 18 patients (6.7%). Staphylococci (39.7%) were the most frequent causative microorganisms, followed by Streptococci (30.0%) and Enterococci (17.8%). Independent predictors of any reinfection were heart failure (HR 3.02, 95% CI 1.42-6.41), peripheral embolization (HR 4.00, 95% CI 1.58-10.17) and implanted pacemakers (HR 3.43, 95% CI 1.25-9.36). Survival rates were 71.1%, 55.2% and 43.3% at respectively 1-, 5- and 10-years follow-up. Independent predictors for mortality were age (HR 1.03, 95% CI 1.01-1.04), diabetes mellitus (HR 2.24, 95% CI 1.46-3.45), hemodialysis (HR 2.70, 95% CI 1.37-5.29), heart failure (HR 1.64, 95% CI 1.19-2.26), stroke (HR 1.73, 95% CI 1.18-2.52), antimicrobial treatment despite surgical indication (HR 5.53, 95% CI 3.59-8.49) and non-Streptococci causative microorganisms (HR 1.84, 95% CI 1.28-2.64). CONCLUSIONS: Contemporary mortality rates of infective endocarditis remain high, irrespective of reinfection. Heart failure, peripheral embolization and presence of a pacemaker were predictors of reinfection.